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Study of β‐cyclodextrin–ketoconazole–tartaric acid multicomponent non‐covalent association by positive and negative ionspray mass spectrometry
Author(s) -
Selva Antonio,
Redenti Enrico,
Ventura Paolo,
Zanol Margherita,
Casetta Bruno
Publication year - 1998
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/(sici)1096-9888(199808)33:8<729::aid-jms687>3.0.co;2-u
Subject(s) - chemistry , deprotonation , protonation , tartaric acid , covalent bond , mass spectrometry , medicinal chemistry , stereochemistry , ion , inorganic chemistry , chromatography , organic chemistry , citric acid
In continuation of studies of multicomponent non‐covalent associations (MCAs) of cyclodextrin (CD) inclusion or host–guest (H–G) complexes of hydrophobic or barely water‐soluble drugs with suitable counter ions, which can dramatically increase the hydrosolubility of the guest drug, was the β‐CD–KC–tartaric acid (TA) MCA, where KC=ketoconazole, an antifungal drug, investigated by ionspray (IS) mass spectrometry (MS) and MS/MS in both the positive and negative ion modes. In the positive IS mode a protonated 1:1:1 β‐CD–KC–TA gaseous species is obtained, which dissociates by the loss of TA upon collisional activation (CA), thus reproducing the same behaviour as observed previously for a β‐CD–terfenadine–TA MCA. Unprecedented results were obtained in the negative ion mode. In particular, deprotonated 1:1:1 β‐CD–KC–TA MCA was detected, which upon CA yielded mainly deprotonated 1:1 β‐CD–TA and tartrate anion. Hence, while a relatively strong interaction binding β‐CD to TA within the MCA parent anion emerges, the fair abundance of tartrate anion could suggest the formation of its neutral complementary fragment, 1:1 β‐CD–KC, a possibly H–G complex not observed as a negatively charged MS/MS fragmentation product. The role of the KC–TA ionic bonding of the neutral MCA appears very pertinent to the study by positive and negative ISMS of the non‐covalent interactions within the gaseous protonated or deprotonated ternary complex thereof. © 1998 John Wiley & Sons, Ltd.